1. Field of the Invention
This invention relates to compositions that are applied directly to mucosal tissue to improve the health thereof and alleviate or eliminate associated complications, and in particularly contemplates a topical cream, solution, gel or suppository that contains phytoestrogens. The disclosed composition is applied directly to any affected or desired mucosal tissue, specifically to the nasal or vaginal mucosal membranes in order to prevent nose bleeds, vaginal dryness and other problems and discomforts related to inadequate hydration or dryness.
2. Prior Art
Mucosal tissue is typically found in orifices of the nasal and rectal passages, the oral cavity and the vagina. Healthy mucosal tissue is moist, and achieving, restoring and/or maintaining proper hydration of these tissues is important. When mucosal tissue is inadequately hydrated, such as may result from a medical or environmental condition. the tissue becomes dry and a person will likely experience some level of inconvenience, pain or discomfort. Commonly encountered complications in the case of nasal passages include epistaxis and rhinorrhagia (nose bleeds), and in the instance of vaginal tissue, dryness and dyspareunia (painful intercourse) may result. Vaginal dryness is often associated with and a recognized complication of menopause and the attendant decrease in a woman's natural hormone levels.
By 2010, an estimated 67 million women in the United States will be above the age of 45, either entering or already in menopause (1). Studies have shown that up to 65% have complaints of vaginal dryness, soreness and pain with intercourse (2,3,4,5). The only treatment that actually alleviates the problem (as opposed to merely treating the symptoms) is vaginal estrogen (6). Vaginal estrogens have also been linked to decreased frequency of urinary tract and bladder infections (7,8) as well as altered vaginal pH which leads to a decreased number of yeast infections (9). Improvements in urinary symptoms such as urinary frequency, urgency and urge incontinence have also been well documented (10). Estrogen receptors have been found on the tissues of the bladder, urethra, and periurethral support tissue (11). Restoring estrogen to the pelvic area increases the tone of these tissues, thereby enhancing urethral closure pressure (which is linked to stress incontinence) (12,13,14), and supports the pelvic organs. Doctors have also recently begun to use vaginal estrogens for interstitial cystitis and other pelvic pain disorders.
Millions of people suffer from chronic recurring nosebleeds in the United States, and epistaxis is responsible for an estimated 450,000 emergency room visits per year (15). The majority of these nosebleeds occur in the anterior (front part) of the nose and are due to dryness, irritation, or trauma. Other than saline nose sprays, to date there have been no other recommended treatments for the prevention of nosebleeds. Certain populations tend to suffer more with anterior nosebleeds, and therefore are easier to include in studies. Patients with hereditary hemorrhagic telangiectasia (HHT, also known as Osler-Weber-Rendau Syndrome) are a case in point, and much research has documented the attempts to decrease the recurrence of nosebleeds in this population. Multiple studies have shown a marked decrease in the severity and number of nosebleeds in this population when treated with estrogens (16-22).
Estrogens (and other steroids) work by binding to nuclear receptors within a cell, and producing a response. Their response can be varied—depending oil the tissue in which they are present. The amount of estrogen needed to effect a desired response has been carefully studied over the years, resulting in some of the estrogen-containing compounds (creams, sprays, ointments, etc.) on the market today. For example, estradiol creams are commonly used to treat the pelvic and vaginal complaints of menopause, and have recently been used to prevent nosebleeds by some otolaryngologists. Recommended dosages have been studied extensively, and are well agreed upon in the literature.
Notwithstanding the efficacy of treating mucosal tissues with human estrogen, it can be appreciated that human estrogen and its derivative therapies are relatively expensive. Animal-derived estrogen compounds are costly as well. It is therefore desirable to provide a composition for treating mucosal membranes that is both effective and inexpensive to produce. Because of their abundance in a variety of plant species distributed around the world, and their well-known estrogenic or pseudoestrogenic character, plant estrogens (phytoestrogens) and related plant compounds are highly desirable alternatives to human or animal estrogen.
Until recently, phytoestrogens had been negatively cast as “alternative” treatments for various ailments such as those associated with menopause, as there was no way of knowing how much phytoestrogen was necessary to effect the same changes as estrogen. Recent studies have been published which quantify the relative binding affinities of estradiol to phytoestrogens, thereby allowing persons skilled in the art to determine exactly how much phytoestrogen is required to make a substance that is bioequivalent to estradiol (23). In the present invention, a natural phytoestrogen composition is disclosed that is bioequivalent to estradiol creams available only by prescription. A variety of plants such as red clover and wild yam contain phytoestrogens or phytoestrogenic compounds that are similar in chemical structure to the estrogens that are present in the human body. Likewise, it is well known in the art that soybeans contain non-steroidal phytoestroen compounds commonly referred to as soy isoflavones. The soy isoflavones, which primarily include daidzen, genistein and glycitein, have been shown to have weak estrogenic activity but have been demonstrated to be beneficial in the treatment of menopausal symptoms.
Black cohosh (Actaeca racemosa) is an herb native to North America that is reportedly effective in alleviating menopausal symptoms such as certain of the vasomotor side effects of menopause including irritability, hot flashes, “edginess”, and depression (24). Black cohosh has been linked to only very rare adverse effects, and it does not have any significant adverse drug reactions (25). It is thought that black cohosh may stimulate estrogen receptors in humans, but it is unclear whether black cohosh is a true phytoestrogen. This invention is to be distinguished from references disclosing phytoestrogenic nutritional or dietary supplements and those otherwise utilizing phytoestrogenic compounds where such compounds are orally ingested. Persons skilled in the art will appreciate that the route of administration is a key factor, as it bears directly on the timeliness and duration of the relief sought. Likewise, this invention may be distinguished from topical creams for use on the outer skin and epithelial tissues. It is readily understood by those skilled in the art that mucosal membranes are significantly distinct in both structure and function.